Recombinant Clostridium botulinum C phage Hemagglutinin components HA-70 type C (HA-70), partial

Function

The hemagglutinin (HA) component of the progenitor toxin protects the structural integrity of botulinum neurotoxin; may increase internalization of the neurotoxin into the bloodstream of the host (PubMed:9421908). The HA component is involved in binding to the upper small intestine through interactions with glycolipids and glycoproteins containing sialic acid moieties (Probable). Whole protein and the HA-53 chain (but not the HA-22-23 chain) bind to bovine mucin; if the mucin is pretreated with neuraminidase (removes the terminal sialic acid of glycoconjugates) mucin binding is decreased (PubMed:19071137). Has higher affinity for alpha-2,3-sialylated oligosaccharides than alpha-2-6 sialylated oligosaccharides (PubMed:22684008)

Subcellular Location

Secreted

Subunit

Botulinum toxins are produced as progenitor toxins of large molecular sizes of 12S (M toxin) and 16S (L toxin). M toxin consists of a non-toxic, non-hemagglutinin component (NTNHA) and the neurotoxin (Probable). L toxin consists of the M toxin and the 3 subcomponents of hemagglutinin (HA) (PubMed:7802661). HA is composed of subcomponents of 70, 33, and 17 kDa (PubMed:7802661). The 70 kDa subcomponent undergoes proteolytic processing and is split into HA-53 (also called HA3b) and HA-22-23 (collectively called HA3a) (PubMed:7802661). Upon crystallization this cleaved component forms a three-lobed trimer of dimers with a hole in the center (PubMed:19071137, PubMed:22684008). Preliminary crystallization studies show a tri-lobed HA-70 where each HA-70 contacts one HA-17 molecule (Probable). The stoichiometry of the whole complex has been modeled as one BoNT/C, one NTNHA, three HA-70, six HA-33 and three HA-17 (By similarity)

• Fujinaga Y. et al. Molecular construction of Clostridium botulinum type C progenitor toxin and its gene organization. — Biochem. Biophys. Res. Commun. (1994)
• Hauser D.F. et al. Organization of the botulinum neurotoxin C1 gene and its associated non-toxic protein genes in Clostridium botulinum C 468. — Mol. Gen. Genet. (1994)
• Fujinaga Y. et al. The haemagglutinin of Clostridium botulinum type C progenitor toxin plays an essential role in binding of toxin to the epithelial cells of guinea pig small intestine, leading to the efficient absorption of the toxin. — Microbiology (1997)
• Nakamura T. et al. Crystal structure of the HA3 subcomponent of Clostridium botulinum type C progenitor toxin. — J. Mol. Biol. (2009)
• Yamashita S. et al. Carbohydrate recognition mechanism of HA70 from Clostridium botulinum deduced from X-ray structures in complexes with sialylated oligosaccharides. — FEBS Lett. (2012)
• Iwasa C. et al. Purification, crystallization and preliminary X-ray analysis of an HA17-HA70 (HA2-HA3) complex from Clostridium botulinum type C progenitor toxin. — Acta Crystallogr. F Struct. Biol. Commun. (2014)